This trial will administer laparoscopic hyperthermic intraperitoneal chemotherapy (HIPEC) to patients with peritoneal carcinomatosis from gastric cancer (GPC) who are receiving standard of care systemic chemotherapy.

Patients with peritoneal carcinomatosis from gastric cancer (GPC) have dismal oncologic outcomes, with median survival duration of 6-12 months and 2-year overall survival rate of < 10%. Despite advancements in systemic therapy, survival remains poor and most patients succumb to the disease within 4-11 months following diagnosis. Therefore, there is a substantial need for novel treatment strategies to improve oncologic outcomes in GPC. The primary intervention is the addition of iterative laparoscopic HIPEC to the ongoing standard systemic chemotherapy regimen (or at least the backbone regimen), based on discussion with their treating medical oncologist. Laparoscopic HIPEC will be performed using a combination of cisplatin (100 mg/m2) and mitomycin C (30 mg total, administered in 2 divided doses of 15 mg each, 45 minutes apart), in 3-liters of normal saline perfusate, at 42°C for 90 minutes, with continuous manipulation of the abdomen to ensure even distribution. Systemic chemotherapy will be administered every two weeks while laparoscopic HIPEC procedures will be performed every 6 weeks in place of the scheduled biweekly systemic therapy cycle. The trial will include a maximum of 3 laparoscopic HIPEC procedures.

Inclusion Criteria:

• Histologically proven, synchronous gastric and/or gastroesophageal junction (Siewert 3) adenocarcinoma with either positive peritoneal cytology (micPC) or macroscopic carcinomatosis (macPC) (stage IV), diagnosed by imaging or laparoscopy or laparotomy.

• Patients must be 18 years of age or older at time of informed consent.

• ECOG performance status of ≤ 2*

  *Note: ECOG PS of 2 is allowed only if debilitation is caused by the gastric cancer and not by other comorbidities.

• Must have normal organ and marrow function following completion of 4-6 months systemic therapy and prior to enrollment as assessed on basic laboratory tests:

Hemoglobin ≥ 8.0 g/dL Leukocytes ≥ 3,000/mcL Absolute neutrophil count ≥ 1,500/mcL Platelet count ≥ 100,000/mcL Total bilirubin < 2mg/dl AST (SGOT) ≤ 2.5 X institutional upper limit of normal (ULN) ALT (SGPT) ≤ 2.5 X institutional ULN Serum creatinine within normal institutional limits

• Patient should have a life expectancy of >6 months per the discretion of the treating surgical oncologist and/or medical oncologist in relation to comorbidities and volume of disease.
• Patients must have received at least 4 months (maximum 6 months) of 1st or 2nd line systemic therapy at the discretion of the treating medical oncologist and/or surgical oncologist and exhibit no evidence of extraperitoneal disease progression prior to enrollment.
• Patients with stable oligometastatic liver only metastasis (≤ 3 lesions, each < 3 cm in maximum dimension), ovarian-only metastases, or lung-only metastases (≤ 5 lesions, each < 1 cm) that are amenable to curative intent surgical resection and/or thermal ablation and/or SBRT will be eligible for enrollment.
• Sexually active fertile subjects and their partners must agree to use highly effective method of contraception prior to study entry and during the course of the study. An additional contraceptive method, such as a barrier method (e.g., condom), is required. In addition, men must agree not to donate sperm and women must agree not to donate eggs (ova, oocyte) for the purpose of reproduction during these same periods.
• Female subjects of childbearing potential must not be pregnant or breastfeeding at screening. Female subjects are considered to be of childbearing potential unless one of the following criteria is met:
• Permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 months of amenorrhea in a woman > 45 years-of-age in the absence of other biological or physiological causes.) Note: Documentation may include review of medical records, medical examination, or medical history interview by study site staff.
• Must have the ability to understand and the willingness to sign a written informed consent document.
• Must be able to read and write in English.

Exclusion Criteria:

• Patients with MSI-H tumors, dMMR, TMB > 30, CPS > 40, POL-E mutation, Claudin 18.2 positive tumors, BRAFV600E, RET fusions, HER-2-neu (3+ on IHC) or positive on FISH will be excluded.
• Extensive retroperitoneal lymph node involvement not amenable to surgical resection during gastrectomy.
• Recurrent large or small bowel obstruction attributable to the cancer (except for gastric outlet obstruction).
• Prior abdominal surgeries that preclude safe and effective laparoscopy/laparoscopic HIPEC.
• Significant ascites requiring repeated drainage for symptomatic relief.
• Other malignancy within the preceding 3 years (except for non-melanoma skin cancer, early-stage prostate cancer, or curatively treated cervical cancer in-situ).
• Patients should have recovered to baseline from any clinically significant adverse events from prior treatment.
• Has acute or chronic active hepatitis B and C virus infection or known history of untreated hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (HCV) (defined as HCV RNA [qualitative]) or HIV infection (see note).

Note: No testing for Hepatitis B, Hepatitis C, or HIV is required unless mandated by local health authority or clinically indicated.

Note: Participants with a history of HIV infection are considered eligible if CD4+ T cell counts are ≥ 350 cells/µL and the patient has had no opportunistic infections in the last 12 months.